1. Field of Invention
This invention relates to methods and devices for improved electrospray nebulization and ionization, specifically to such electrospray nebulizers which are used for the production and introduction of gas-phase ions at atmospheric pressure into mass spectrometers and other gas-phase ion analyzers and detectors.
2. Discription of Prior Art
Ion sources that utilize high electrical potentials to generate ions at or near atmospheric pressure; such as, atmospheric pressure discharge ionization and chemical ionization, and electrospray ionization; have low sampling efficiency through conductance or transmission apertures, where less than 1% [often less than 1 ion in 10,000] of the ion current emanating from the ion source make it into the lower pressure regions of the present interfaces for mass spectrometry. Thereafter, scientists have devised several means of delivering and transferring gas-phase ions from atmospheric pressure sources into the vacuum system of mass spectrometers, such as, using lower flow electrostatic sprayers to form very small droplets [referred to as nanospray], using increased heating of the aerosols to generate more gas-phase ions, increasing the sampling diameter of the sampling aperture at the atmospheric-lower pressure interface, and using electrostatic, electrodynamic, or aerodynamic lens at atmospheric and low pressure to focus highly charged liquid jets, aerosols of droplets and ion clusters, and gas-phase ions.
Lens for Low Pressure Sources: Liquid Metal Ion and Low Pressure Electrospray Ion Sources
Electrodes or lens have been disclosed to increase the ion signal of electrospray sources and liquid metal ion sources operated at lower pressures—for example, in U.S. Pat. No. 4,318,028 to Perel et al. (1982), Mahoney et al. (1987), Lee et al. (1988, 1989), and U.S. Pat. No. 7,211,805 to Kaga et al (2007). Our own patents U.S. Pat. Nos. 5,838,002 (1998), 6,278,111 B1 (2001), and World patent 98/07505 (1998) describes a sub-atmospheric source comprised of a concentric tube which surrounds the end of the electrospray capillary which was used to electrically stabilize the liquid cone-jet, directing the liquid jet into a heated high pressure region where the jet broke up into small droplets and where gas-phase ions and ion clusters were formed. This approach proved feasible but it was found to difficult to control the collection and focusing of ions formed in this higher-pressure region due to the electrical breakdown of the gases.
Lens for Atmospheric Pressure Electrospray Sources: Between Sprayer and Aperture or Inlet
Several types of ring or planar electrodes positioned between the sprayer and an inlet aperture have been proposed to focus ions and charged droplets for example—Olivares et al. (1987) disclosed a focusing ring located downstream of the electrospray sprayer; U.S. Pat. No. 5,306,910 to Jarrell et al. (1994) disclosed a gird which is operated with an oscillating electrical potential to form gas-phase ions from highly charge droplets, while allowing the electrospray needle and entrance aperture to remain at ground potential, however, most of the droplets would impact on the grid as they pass through the grid, not making it into the inlet aperture; Feng et al. (2002) describes a series of annular electrodes downstream of an induction electrode used to guide charged droplets; Alousi et al. (2002) describes a lens between the electrospray needle and the entrance aperture dividing the ion source into two discrete areas, an area for the creation of highly charged droplets and gas-phase ions and a drift region with an electrical gradient across the area, leading to an increase of 2-10 fold in the signal intensity however, most of the ion current from the sprayer was deposited on the lens; and U.S. Pat. No. 7,071,465 to Hill, Jr. et al. (2006) disclosed placing the electrospray needle inside an ion mobility spectrometer comprised of a series of ring electrodes.
World patent 03/010794 A2 to Forssmann et al. (2003) disclosed a series of annular electrodes for ion acceleration and then subsequent ion focusing in front of the inlet aperture, similar to the device described by Jarrell et al. (1994). Jarrell et al.'s device utilize an oscillatory potential while Forssmann et al.'s device utilizes a direct current potential to first accelerate charged drops away from the electrospray needle, through an aperture in an accelerating electrode [or through an accelerating grid in Jarrell et al.'s device], and then into a focusing region. In both cases, droplets are accelerated away from an electrospray needle and travel up a potential gradient into a focusing region due to their momentum. Droplets and any gas-phase ions resulting from the breakup of the droplets would more than likely impact on the accelerating electrodes due to the diverging electrostatic fields along the axis of the electrodes.
Lens for Atmospheric Pressure Ion Sources: Lens at Electrospray Nebulizer and Discharge Source
Several types of ring or planar electrodes at the sprayer have been proposed to focus ions and charged droplets at atmospheric pressure. U.S. Pat. No. 4,531,056 to Labowsky et al. (1985) disclosed a perforated diaphragm used to direct the flow of a gas over an electrospray needle to aid in the evaporation of highly charged droplets emanating from the needle and sweep away gas-phase solvent molecules from the area in front of the inlet aperture. In addition, the diaphragm was used to stabilize the position of the needle to direct the liquid jet through a center aperture in the diaphragm leading into a desolvation or ionization region.
For discharge ion sources, such as atmospheric pressure ionization of gases and atmospheric pressure chemical ionization, several types of lenses at the discharge source have been proposed and/or implemented—for example, U.S. Pat. No. 6,147,345 to Willoughby (2000) disclosed an electrospray ion source comprised of a discharge needle, a counter electrode, a lens, and a gas source for seeding the liquid emerging from an electrospray needle with counter ions; and U.S. Pat. No. 6,949,741 to Cody et al. (2005) and U.S. Pat. No. 7,112,785 to Larame et al. (2006), and now marketed as DART™ (Direct Analysis in Real Time) by JEOL-USA, Inc. (Peabody, Mass., www.jeol.com) and IONSENSE, Inc. (Peabody, Mass.; www.ionsense.com), disclosed an atmospheric discharge source comprised of a discharge needle, a counter electrode, and a field-free reaction chamber. Our own U.S. Pat. Nos. 6,888,132 (2005), 7,095,019 (2006), and 7,253,406 (2007), all to Sheehan et al. disclosed a remote reagent ion source comprised of a laminated high-transmission lens for ionizing gas-phase species in a field-free or near field-free reaction region; and U.S. provisional patent application 60/724,389 to Karpetsky et al. (2005) marketed and introduced for sale in June 2007 at the 55th ASMS Conference on Mass Spectrometry and Allied Topics (Indianapolis, Ind.), as Remote Reagent Ion Generator (RRIG) by Chem-Space Associates, Inc. (Pittsburgh, Pa.; www.lcms.com), disclosed a remote reagent chemical ionization source comprised of a discharge needle, counter electrode, and a saddle electrode coupled to a field-free transfer region for ionization of gas-phase species in a field-free or near field-free reaction region.
Several types of electrostatic lens or electrodes at the tip of the electrospray needle have been proposed, for example—Schneider et al. (2001, 2002) disclosed a ring shaped electrode incorporated near the tip of the electrospray needle which increased the detected ion signal and the stability of the signal and at the same time decreasing the dependence of the ion signal on the sprayer position; U.S. Pat. No. 7,067,804 to Chen et al. (2006) and G.B. patent application 2428514 to Syms (2007) both disclosed an individual lens and a series of lenses to shape the electric fields in the atmospheric pressure region to cause more ions from the source to reach a downstream ion detector; U.S. Pat. No. 6,462,337 to Li et al. (2002) disclosed an auxiliary electrode so as to increase the electric field gradient from the capillary to the inlet thereby focusing and decreasing the beam divergence; U.S. Pat. No. 6,992,299 to Lee et al. (2006) disclosed an aerodynamic ion focusing system that uses a high-velocity converging gas flow to focus a diverging aerosol ion plume; and U.S. Pat. No. 7,015,466 to Takats, et al. (2006) disclosed aerodynamic desolvation and focusing of the electrospray plume.
Two types of electrospray nebulizers with lens have been disclosed and are available for sale. An electrospray probe manufactured and sold by Thermo Scientific (San Jose, Calif.; www.thermo.com), H-ESI™ (Heated Electrospray Ionization) discloses aerodynamic desolvation and focusing using a supersonic flow of gas through a tube surrounding the electrospray needle. While U.S. Pat. Nos. 6,998,605 (2006), 7,041,966 (2006), 7,259,368 (2007), all to Frazer et al. disclosed an electrospray assembly at or near ground potential. The sample is introduced into the ionization chamber from an electrospray assembly at approximately ground potential. Two electrodes are provided within the chamber such that three electric fields are generated, a first field extending from the electrospray assembly to the first electrode, a second field extending from the second electrode to the first electrode, and a third field extending from the second electrode to the vacuum interface. Ionization takes place between the electrospray assembly and the second electrode. Ions are forces to travel through the three fields by a concurrent flow of gas and the electric fields generated by the electrodes and the vacuum interface, before entering the vacuum chamber. This design is incorporated into a multimode (electrospray and atmospheric pressure chemical ionization) source, G1978A™, offered by Agilent Technologies, Inc. (Santa Clara, Calif.; www.agient.com).
Nevertheless atmospheric lens, electrodes, and grids in electrospray ion sources heretofore known suffer from a number of disadvantages:
(a) Electrospray nebulizers where lens and electrodes are disposed in the ionization region where gas-phase ions are formed from charged droplets, droplets and ion-clusters are lost due to impaction on these structures.
(b) The use of lenses in the ionization region to focus ions and charged droplets leads to the dispersion of these ions as they past through each subsequent lens, such as the dispersion at the entrance to capillary tubes or apertures. Ions, droplets, and ion-clusters can be lost due to these dispersive forces.
(c) The use of multiple lenses in the ionization region requires the use of greater and greater potentials on the lens to focus the ions from one region to another. This creates a large electrostatic gradient across the ionization region which can lead to possible electrostatic breakdown of the gases in the region, the requirement for high voltage power supplies, and dispersive loses as the ions pass through the lens. In essence, the more you try to focus ions with larger potentials the more they will disperse as they leave the area of large potentials and enter areas of lower or no potentials, such as passing through an aperture or into a tube.
(d) If one uses high velocity flows of gas to focus ions there is a need for a large volume of gas and since larger droplets are influences more so than smaller droplets and gas-phase ions by these viscous forces, larger droplets are lost due to impaction on lens and walls of the ionization chamber and are thereby lost from the gas-phase ion production process.